Amphotericin B, a potent antifungal agent, is a member of a class of compounds known as polyene macrolide antibiotics. These compounds are characterized by a large lactone ring which includes a chain of conjugated double bonds.
Amphotericin B, and its method of preparation from Streptomyces nodosus, is disclosed by Dutcher et al. in U.S. Pat. No. 2,908,611, issued Oct. 13, 1959. The structure of amphotericin B is now known to be ##STR1##
Nystatin is another member of the group of antibiotics known as polyene macrolides. Mendelsohn, in U.S. Pat. No. 3,509,255, issued Apr. 28, 1970, discloses a process for the purification of nystatin which comprises extracting crude nystatin with acetone which is saturated with sodium iodide, sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, or mixtures thereof, and precipitating purified crystalline nystatin from the extract by the displacement of acetone with water.
The solubility characteristics of nystatin and ampotericin B differ markedly. While it is known that polyene macrolides have a very limited solubility in common organic solvents, nystatin is, in general, substantially more soluble than amphotericin B, specifically in such commercially attractive solvents as acetone and methanol. The solubility of amphotericin B in acetone is about 95 .gamma./ml and in methanol about 940 .gamma./ml. The problems caused by this lack of solubility are well known to those who work with processes for the isolation and extraction of amphotericin B.
As recognized by Dutcher et al. in U.S. Pat. No. 2,908,611 amphotericin B does have good solubility in dimethylformamide and glacial acetic acid. Furthermore, the solubility of amphotericin B in the lower alkanols can be increased by the addition of acid or strong base. In view of the above, it is not surprising that the prior art has relied heavily on the use of dimethylformamide in processes for the purification of amphotericin B.